5-HT(3)受体拮抗剂格拉司琼对大鼠霍乱毒素诱导的5-HT释放的抑制作用

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Turvill JL, Connor P, Farthing MJ

5-HT(3)受体拮抗剂格拉司琼对大鼠霍乱毒素诱导的5-HT释放的抑制作用

中国药物学杂志，2000年7月;130(5):1031-6。

PubMed ID

10882387 (PubMed视图

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摘要

1.促分泌剂5-羟色胺(5-HT)与霍乱的病理生理学有关。霍乱毒素暴露后肠染色质细胞释放的5-HT被认为是非神经性(5-HT(2)依赖性)和神经性(5-HT(3)依赖性)介导的水和电解质分泌。通过阻止5-HT的释放可以减少ct的分泌。肠色素细胞拥有大量受体，在基础条件下，调节5-HT的释放。2.这些受体包括基底外侧5-HT(3)受体，已知其激活可增强5-HT的释放。3.到目前为止，5-HT(3)受体拮抗剂(如格拉司琼)被认为通过阻断分泌性肠神经元上的5-HT(3)受体来抑制霍乱毒素诱导的液体分泌。相反，我们假设它们通过抑制霍乱毒素诱导的肠染色质细胞脱颗粒而起作用。 4. Isolated intestinal segments in anaesthetized male Wistar rats, pre-treated with granisetron 75 microg kg(-1), lidoocaine 6 mg kg(-1) or saline, were instilled with a supramaximal dose of cholera toxin or saline. Net fluid movement was determined by small intestinal perfusion or gravimetry and small intestinal and luminal fluid 5-HT levels were determined by HPLC with fluorimetric detection. 5. Intraluminal 5-HT release was proportional to the reduction in tissue 5-HT levels and to the onset of water and electrolyte secretion, suggesting that luminal 5-HT levels reflect enterochromaffin cell activity. 6. Both lidocaine and granisetron inhibited fluid secretion. However, granisetron alone, and proportionately, reduced 5-HT release. 7. The simultaneous inhibition of 5-HT release and fluid secretion by granisetron suggests that 5-HT release from enterochromaffin cells is potentiated by endogenous 5-HT(3) receptors. The accentuated 5-HT release promotes cholera toxin-induced fluid secretion.

引用本文的药物库数据

药物靶点

药物	目标	种类	生物	药理作用	行动
Granisetron	5-羟色胺受体3A	蛋白质	人类	是的	拮抗剂	细节